Spaced training induces normal long-term memory in CREB mutant mice

Kogan, J. H., Frankland, P. W., Blendy, J. A., Coblentz, J., Marowitz, Z., Schutz, G., Silva, A. J. (January 1997) Spaced training induces normal long-term memory in CREB mutant mice. Current Biology, 7 (1). pp. 1-11. ISSN 0960-9822

URL: http://www.ncbi.nlm.nih.gov/pubmed/8999994
DOI: 10.1016/S0960-9822(06)00022-4

Abstract

BACKGROUND: The cAMP responsive element binding protein (CREB) is a transcription factor the activity of which is modulated by increases in the intracellular levels of cAMP and calcium. Results from studies with Aplysia, Drosophila and mice indicate that CREB-activated transcription is required for long-term memory. Furthermore, a recent study found that long-term memory for olfactory conditioning can be induced with a single trial in transgenic Drosophila expressing a CREB activator, whereas in normal flies, with presumably lower CREB-mediated transcription levels, conditioning requires multiple spaced trials. This suggests that CREB-mediated transcription is important in determining the type of training required for long-term memory of olfactory conditioning in Drosophila. Interestingly, studies with cultured Aplysia neurons indicated that removing a CREB repressor promoted the formation of long-term facilitation, a cellular model of non-associative memory. RESULTS: Here, we have confirmed that mice lacking the alpha and Delta CREB proteins (CREBalphaDelta-) have abnormal long-term, but not short-term, memory, as tested in an ethologically meaningful task. Importantly, additional spaced training can overcome the profound memory deficits of CREBalphaDelta- mutants. Increasing the intertrial interval from 1 to 60 minutes overcame the memory deficits of the CREBalphaDelta- mice in three distinct behavioral tasks: contextual fear conditioning, spatial learning and socially transmitted food preferences. CONCLUSIONS: Previous findings and results presented here demonstrate that CREB mutant mice have profound long-term memory deficits. Importantly, our findings indicate that manipulations of CREB function can affect the number of trials and the intertrial interval required for committing information to long-term memory. Remarkably, this effect of CREB function is not restricted to simple conditioning tasks, but also affects complex behaviours such as spatial memory and memory for socially transmitted food preferences.

Item Type: Paper
Uncontrolled Keywords: Animals Conditioning (Psychology)/physiology Cyclic AMP Response Element-Binding Protein/ genetics/physiology Female Food Preferences/physiology Male Maze Learning/physiology Memory/ physiology Mice Mice, Mutant Strains Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Time Factors
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > transcription factor > CREB
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > transcription factor > Cyclic AMP
organism description > animal behavior > memory
CSHL Authors:
Communities: CSHL labs
Depositing User: Kathleen Darby
Date: 1 January 1997
Date Deposited: 08 May 2014 18:21
Last Modified: 08 May 2014 18:21
Related URLs:
URI: http://repository.cshl.edu/id/eprint/29968

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